X-linked agammaglobulinemia

With X-linked agammaglobulinemia, or XLA for short, gamma globulin is another name for immunoglobulin, which is another name for antibodies, a- means without, and -emia refers to the blood.

So this is a disease where there aren’t any antibodies in the blood, and X-linked means that it’s caused by a gene mutation on the X chromosome.

Now, normally, immunoglobulins are secreted into the blood by plasma cells, which are fully matured or differentiated B cells, a type of immune cell.

Way before that ever happens, though, those B cells start out in the bone marrow as pluripotent stem cells, pluripotent meaning that they can develop into a number of different types of cells.

But to become a B cell, first that pluripotent stem cell differentiates into a lymphoid precursor cell, then a pro-B cell, then a pre-B cell, then an immature B cell which migrates from the bone marrow to the spleen, where it becomes a mature or naive B cell, which after being exposed to the right antigen, moves into the blood or lymph and becomes an antibody-secreting plasma cell.

In XLA, this maturation process stops at the pre-B cell stage.

Why does it do that? Well, by the immature B cell stage, it has a B cell receptor, which is a membrane-bound antibody, specifically an immunoglobulin M or IgM.

But in the Pre- and Pro-B cell stages, this B cell receptor’s still being assembled, once it’s finished, it’s made up of heavy chain and light chain protein subunits, and the heavy chains are put together first.

Since it hasn’t been fully assembled yet, this IgM’s known as a pre-B cell receptor.

Now, an enzyme called bruton’s tyrosine kinase is super important for both the development and normal functioning of the B cell receptor.